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Short-term treatment of equine wounds with orf virus IL-10 and VEGF-E dampens inflammation and promotes repair processes without accelerating closure.
Abstract: Healing is delayed in limb wounds relative to body wounds of horses, partly because of sustained inflammation and inefficient angiogenesis. In laboratory animals, proteins derived from orf virus modulate these processes and enhance healing. We aimed to compare immune cell trafficking and the inflammatory, vascular, and epidermal responses in body and limb wounds of horses and then to investigate the impact of orf virus interleukin-10 and vascular endothelial growth factor-E on these processes. Standardized excisional wounds were created on the body and forelimb of horses and their progression monitored macroscopically until healed. Tissue samples were harvested to measure the expression of genes regulating inflammation and repair (quantitative polymerase chain reaction) and to observe epithelialization (histology), innate immune cell infiltration, and angiogenesis (immunofluorescence). Delayed healing of limb wounds was characterized by intensified and extended pro-inflammatory signaling and exacerbated innate immune response, concomitant with the absence of anti-inflammatory eIL-10. Blood vessels were initially more permeable and then matured belatedly, concomitant with retarded production of angiogenic factors. Epithelial coverage was achieved belatedly in limb wounds. Viral proteins were administered to wounds of one body and one limb site/horse at days 1-3, while wounds at matching sites served as controls. Treatment dampened pro-inflammatory gene expression and the innate immune response in all wounds. It also improved angiogenic gene expression, but primarily in body wounds, where it altered blood vessel density and myofibroblast persistence. Moreover, the viral proteins increased epithelialization of all wounds. The short-term viral protein therapy did not, however, improve the healing rate of wounds in either location, likely due to suboptimal dosing. In conclusion, we have further detailed the processes contributing to protracted healing in limb wounds of horses and shown that short-term administration of viral proteins exerts several promising though transient effects that, if optimized, may positively influence healing.
© 2016 by the Wound Healing Society.
Publication Date: 2016-10-18 PubMed ID: 27681311DOI: 10.1111/wrr.12488Google Scholar: Lookup The Equine Research Bank provides access to a large database of publicly available scientific literature. Inclusion in the Research Bank does not imply endorsement of study methods or findings by Mad Barn.
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.
This research article investigates the impact of proteins derived from orf virus on the healing of body and limb wounds in horses. Specifically, the effects of orf virus interleukin-10 and vascular endothelial growth factor-E on inflammation, vascular, and epidermal responses have been considered. Although the short-term therapy did not improve overall healing rate, it showed promising effects on inflammation and repair processes.
Objective of the Research
- The objective of the research was to understand the differential healing patterns in body and limb wounds of horses, specifically focusing on the role of inflammation and inefficient angiogenesis.
- The aim was further extended to researching the effects of orf virus-interleukin-10 and vascular endothelial growth factor-E on wound healing processes.
Research Methodology
- The researchers created standardized excisional wounds on the bodies and forelimbs of horses and monitored their healing progression.
- They examined tissue samples to measure gene expression related to inflammation and repair, and used immunofluorescence to observe innate immune cell infiltration and angiogenesis.
- To assess the effects of the viral proteins, these were applied to the wounds at specific intervals while the healing progress of control wounds was also documented.
Findings of the Research
- The study found that limb wounds in horses took longer to heal due to heightened and prolonged pro-inflammatory signaling and an exacerbated innate immune response.
- It was observed that blood vessels in these limb wounds were initially more permeable and matured tardily, which could be due to retarded angiogenic factors.
- The limb wounds also achieved epithelial coverage later than the body wounds.
- Applying the viral proteins to the wounds resulted in dampened pro-inflammatory gene expression and improved angiogenic gene expression in all wounds, primarily in body wounds.
- Despite these improvements, the overall healing rate of wounds did not increase, suggesting that the dose of the proteins may need to be optimized.
Conclusion
- In conclusion, the research shed light on the different contributing processes to the healing of limb wounds in horses.
- It demonstrated that the short-term administration of orf virus-derived proteins could potentially influence wound healing positively if the dosing is optimized.
Cite This Article
APA
Bodaan CJ, Wise LM, Wakelin KA, Stuart GS, Real NC, Mercer AA, Riley CB, Theoret C.
(2016).
Short-term treatment of equine wounds with orf virus IL-10 and VEGF-E dampens inflammation and promotes repair processes without accelerating closure.
Wound Repair Regen, 24(6), 966-980.
https://doi.org/10.1111/wrr.12488 Publication
Researcher Affiliations
- Institute of Veterinary, Animal and Biomedical Sciences, Massey University, Palmerston North.
- Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.
- Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.
- Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.
- Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.
- Department of Microbiology and Immunology, University of Otago, Dunedin, New Zealand.
- Institute of Veterinary, Animal and Biomedical Sciences, Massey University, Palmerston North.
- Institute of Veterinary, Animal and Biomedical Sciences, Massey University, Palmerston North.
- Comparative Tissue Healing Laboratory, Department of Veterinary Biomedical Sciences, Faculty of Veterinary Medicine, University of Montreal, Montreal, Canada.
MeSH Terms
- Animals
- Cells, Cultured
- Extremities / injuries
- Extremities / pathology
- Extremities / virology
- Gene Expression Regulation
- Horses
- Humans
- Inflammation / genetics
- Inflammation / pathology
- Inflammation / therapy
- Inflammation / virology
- Interleukin-10 / genetics
- Interleukin-10 / metabolism
- Male
- Neovascularization, Physiologic
- Orf virus / genetics
- Viral Proteins / genetics
- Viral Proteins / metabolism
- Wound Healing
- Wounds and Injuries / genetics
- Wounds and Injuries / therapy
Citations
This article has been cited 14 times.- Lessiak U, Melchert M, Walter I, Kummer S, Nell B, Tschulenk W, Pratscher B. Isolation-protocol, characterization, and in-vitro performance of equine umbilical vein endothelial cells. Front Vet Sci 2024;11:1421946.
- Reider IE, Lin E, Krouse TE, Parekh NJ, Nelson AM, Norbury CC. γδ T Cells Mediate a Requisite Portion of a Wound Healing Response Triggered by Cutaneous Poxvirus Infection. Viruses 2024 Mar 10;16(3).
- Lessiak U, Pratscher B, Tichy A, Nell B. Bevacizumab Efficiently Inhibits VEGF-Associated Cellular Processes in Equine Umbilical Vein Endothelial Cells: An In Vitro Characterization. Vet Sci 2023 Oct 26;10(11).
- Jørgensen E, Bjarnsholt T, Jacobsen S. Biofilm and Equine Limb Wounds. Animals (Basel) 2021 Sep 27;11(10).
- Chen L, Zhang L, Zhang H, Sun X, Liu D, Zhang J, Zhang Y, Cheng L, Santos HA, Cui W. Programmable immune activating electrospun fibers for skin regeneration. Bioact Mater 2021 Oct;6(10):3218-3230.
- Hu Y, Wang X, Wei Y, Liu H, Zhang J, Shen Y, Cao J. Functional Inhibition of Natural Killer Cells in a BALB/c Mouse Model of Liver Fibrosis Induced by Schistosoma japonicum Infection. Front Cell Infect Microbiol 2020;10:598987.
- Wise LM, Stuart GS, Sriutaisuk K, Adams BR, Riley CB, Theoret CL. Anti-fibrotic Actions of Equine Interleukin-10 on Transforming Growth Factor-Beta1-Stimulated Dermal Fibroblasts Isolated From Limbs of Horses. Front Vet Sci 2020;7:577835.
- Wise LM, Stuart GS, Jones NC, Fleming SB, Mercer AA. Orf Virus IL-10 and VEGF-E Act Synergistically to Enhance Healing of Cutaneous Wounds in Mice. J Clin Med 2020 Apr 11;9(4).
- Yaron JR, Zhang L, Guo Q, Burgin M, Schutz LN, Awo E, Wise L, Krause KL, Ildefonso CJ, Kwiecien JM, Juby M, Rahman MM, Chen H, Moyer RW, Alcami A, McFadden G, Lucas AR. Deriving Immune Modulating Drugs from Viruses-A New Class of Biologics. J Clin Med 2020 Mar 31;9(4).
- Muhsen M, Protschka M, Schneider LE, Müller U, Köhler G, Magin TM, Büttner M, Alber G, Siegemund S. Orf virus (ORFV) infection in a three-dimensional human skin model: Characteristic cellular alterations and interference with keratinocyte differentiation. PLoS One 2019;14(1):e0210504.
- Kamus LJ, Theoret C, Costa MC. Use of next generation sequencing to investigate the microbiota of experimentally induced wounds and the effect of bandaging in horses. PLoS One 2018;13(11):e0206989.
- Wise LM, Stuart GS, Real NC, Fleming SB, Mercer AA. VEGF Receptor-2 Activation Mediated by VEGF-E Limits Scar Tissue Formation Following Cutaneous Injury. Adv Wound Care (New Rochelle) 2018 Aug 1;7(8):283-297.
- Alkharsah KR. VEGF Upregulation in Viral Infections and Its Possible Therapeutic Implications. Int J Mol Sci 2018 Jun 1;19(6).
- Wise LM, Bodaan CJ, Stuart GS, Real NC, Lateef Z, Mercer AA, Riley CB, Theoret CL. Treatment of limb wounds of horses with orf virus IL-10 and VEGF-E accelerates resolution of exuberant granulation tissue, but does not prevent its development. PLoS One 2018;13(5):e0197223.
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